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The Dutch Fabry cohort: Diversity of clinical manifestations and Gb3 levels

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Summary

Background: Fabry disease (OMIM 301500) is an X-linked lysosomal storage disorder with characteristic vascular, renal, cardiac and cerebral complications. Globotriaosylceramide (Gb3) accumulates in Fabry patients as a result of α-galactosidase A deficiency. The phenotypic variability is high, but the relationship between clinical symptoms in individual Fabry patients has not been uniformly documented. Also, the relation between the most prominent biochemical abnormalities, elevated Gb3 levels in plasma and urine, and clinical symptoms is not firmly established. Methods: Clinical and biochemical characteristics of 96 (25 deceased) Dutch Fabry patients were collected retrospectively and before the initiation of enzyme therapy. Results: Clinical assessment revealed that median life expectancy was 57 years for male and 72 years for female patients. Cerebral complications, acroparaesthesias and gastrointestinal complications, but not cardiac and auditory complications, were all seen more frequently in male than female patients. Glomerular filtration rate (GFR) was highly variable in male patients, including 2 patients with GFR < 30 ml/min, but median GFR did not differ between males and females (103 and 101 ml/min, respectively). Hyperfiltration was more frequently observed in the female patient group. Microalbuminuria was present in 60% of males and 45% of females. No specific pattern of combined symptoms existed except for a relationship between left ventricular hypertrophy (LVH) and cerebral complications (males 36%, females 32%), or proteinuria (males 35%, females 31%). Gb3 was found to be more elevated in plasma samples from male (n = 26; median 6.27 μmol/L (1.39–9.74)) than female Fabry patients (n = 37; median 2.16 (0.77–4.18)). This was also observed for urinary Gb3: males (n = 22) median 1851 nmol/24 h (40–3724); females (n = 29) median 672 (86–2052). Plasma and urinary Gb3 levels correlated with each other in both males (r = 0.4, p = 0.05) and females (r = 0.4, p = 0.03), but no correlation between elevated Gb3 levels and clinical symptoms could be detected. Conclusion: Analysis of the characteristics of the Dutch Fabry cohort has revealed that a limited relationship between various disease manifestations exists and that individual symptoms do not correlate with elevated urinary or plasma Gb3 levels, limiting their value as surrogate disease markers.

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Abbreviations

αGal A:

α-galactosidase A

BPI:

Brief Pain Inventory

CVA:

cerebrovascular accident

ECG:

electrocardiogram

ERPF:

effective renal plasma flow

FF:

filtration fraction

Gb3 :

globotriaosylceramide

GFR:

glomerular filtration rate

HPLC:

high-pressure liquid chromatography

K/DOQI:

kidney disease outcomes quality initiative

LVH:

left ventricular hypertrophy

LVMass:

left ventricular mass

MRI:

magnetic resonance imaging

MSSI:

Mainz severity score index

PTA:

pure-tone average

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Authors and Affiliations

  1. Department of Internal Medicine/Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

    A. C. Vedder & G. E. Linthorst

  2. Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands

    A. C. Vedder, G. E. Linthorst, M. J. van Breemen, J. E. M. Groener, A. Strijland & J. M. F. G. Aerts

  3. Department of Internal Medicine/Nephrology, Academic Medical Center, Amsterdam, The Netherlands

    F. J. Bemelman

  4. Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands

    M. M. A. M. Mannens

  5. Department of Internal Medicine/Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

    C. E. M. Hollak

Authors
  1. A. C. Vedder
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  2. G. E. Linthorst
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  3. M. J. van Breemen
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  4. J. E. M. Groener
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  5. F. J. Bemelman
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  6. A. Strijland
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  7. M. M. A. M. Mannens
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  8. J. M. F. G. Aerts
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  9. C. E. M. Hollak
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Corresponding author

Correspondence to C. E. M. Hollak.

Additional information

Communicating editor: Joe Clarke

Competing interests: None declared

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Vedder, A.C., Linthorst, G.E., van Breemen, M.J. et al. The Dutch Fabry cohort: Diversity of clinical manifestations and Gb3 levels. J Inherit Metab Dis 30, 68–78 (2007). https://doi.org/10.1007/s10545-006-0484-8

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  • DOI: https://doi.org/10.1007/s10545-006-0484-8

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